Understanding responses by changes in land use and land cover (LULC) and climate over the past decades on streamflow in the upper Blue Nile River basin is important for water management and water resource planning in the Nile basin at large. This study assesses the long-term trends of rainfall and streamflow and analyses the responses of steamflow to changes in LULC and climate in the upper Blue Nile River basin. Findings of the Mann-Kendall (MK) test indicate statistically insignificant increasing trends for basin-wide annual, monthly, and long rainy-season rainfall but no trend for the daily, short rainy-season, and dry season rainfall. The Pettitt test did not detect any jump point in basin-wide rainfall series, except for daily time series rainfall. The findings of the MK test for daily, monthly, annual, and seasonal streamflow showed a statistically significant increasing trend. Landsat satellite images for 1973, 1985, 1995, and 2010 were used for LULC change-detection analysis. The LULC change-detection findings indicate increases in cultivated land and decreases in forest coverage prior to 1995, but forest area increases after 1995 with the area of cultivated land that decreased. Statistically, forest coverage changed from 17.4% to 14.4%, by 12.2%, and by 15.6%, while cultivated land changed from 62.9% to 65.6%, by 67.5%, and by 63.9% from 1973 to 1985, in 1995, and in 2010, respectively. Results of hydrological modelling indicate that mean annual streamflow increased by 16.9% between the 1970s and 2000s due to the combined effects of LULC and climate change. Findings on the effects of LULC change on only streamflow indicate that surface runoff and base flow are affected and are attributed to the 5.1% reduction in forest coverage and a 4.6% increase in cultivated land areas. The effects of climate change only revealed that the increased rainfall intensity and number of extreme rainfall events from 1971 to 2010 significantly affected the surface runoff and base flow. Hydrological impacts by climate change are more significant as compared to the impacts of LULC change for streamflow of the upper Blue Nile River basin.